Sickle cell disease (SCD) is a common disorder among African-Americans and other minority populations that is characterized by chronic anemia and episodic "vaso-occlusive" crises. Acute pulmonary disease, descriptively termed "acute chest syndrome" (ACS), is one of these events. ACS is a common cause of hospitalization for affected individuals, and it is the most common cause of death clue to SCD. Despite the significance of ACS, its treatment is supportive and often inadequate. Glucocorticoids inhibit several ostensible steps in the pathogenesis of ACS. Specifically, steroids attenuate the inflammatory process, inhibit the enzyme sPLA2, and prevent cytokine-induced expression of adhesion molecules by endothelial cells. A pilot study showed that the glucocorticoid dexamethasone had therapeutic benefit for ACS. This proposal describes a clinical investigation to test rigorously the efficacy of dexamethasone for ACS. The specific aims of this project are to show that dexamethasone safely decreases the morbidity of ACS using objective measures and to determine whether dexamethasone therapy prevents adverse subacute effects on pulmonary function. These aims are achieved by a prospective, randomized, double-blind, placebo-controlled clinical trial. Subjects will receive standard supportive therapy for ACS, and they will be randomly assigned to receive either oral dexamethasone or placebo. Efficacy will be assessed by comparing the effect of therapy on the length of hospitalization, the duration of supplemental oxygen therapy, the number of transfusion events, a quantitative measure of opioid use, and the duration of fever. Effect of treatment on pulmonary function and radiographic resolution will be compared one month after discharge. Subjects will also be monitored for potential adverse effects of the study medication. The Southwestern Comprehensive Sickle Cell Center has the expertise and resources to conduct this proposed inter-center investigation, and it will generate the highest quality of clinical evidence to improve the care of individuals with SCD and ACS.